The proposed research training plan describes a unique synthetic approach the pentacyclic spiro-oxindole natural product citrinadin B that will be extended to the synthesis of the related compound citrinadin A. Their complex architectures and reported biological activites as cytotoxic agents against murine leukemia cells and human epidermoid carcinoma have made the citrinadins popular synthetic targets since their isolation and structural elucidation in 2004 and 2005. The proposed synthetic route to the citrinadins will capitalize on the use of methoxypyridines as surrogates for piperidines in the synthesis of complex alkaloids. The synthetic plan hinges on the development of a novel cascade annulation process involving a Lewis acid-mediated aza-Payne rearrangement and aziridinium-opening pyridone alkylation to rapidly assemble the densely functionalized C, D and E rings of the citrinadins. Substrate-directed elaboration of the E ring of the citrinadins will enable access to either citrinadin congener from a late stage intermediate. Diastereoselective oxidative rearrangement and transition metal-mediated cross-coupling will establish the spiro-oxindole motif and C7 substitution of the citrinadins. This route will provide access to either enantiomer o the central core of the citrinadins through Sharpless asymmetric epoxidation of an achiral tetrasubstituted allylic alcohol. The execution of this research strategy will provide sufficient material for further biological evaluation of the citrinadins.